Nucleic acid binding proteins affect the subcellular distribution of phosphorothioate antisense oligonucleotides.
Nucleic Acids Res
; 45(18): 10649-10671, 2017 Oct 13.
Article
em En
| MEDLINE
| ID: mdl-28977508
ABSTRACT
Antisense oligonucleotides (ASOs) are versatile tools that can regulate multiple steps of RNA biogenesis in cells and living organisms. Significant improvements in delivery, potency, and stability have been achieved through modifications within the oligonucleotide backbone, sugar and heterocycles. However, these modifications can profoundly affect interactions between ASOs and intracellular proteins in ways that are only beginning to be understood. Here, we report that ASOs with specific backbone and sugar modifications can become localized to cytoplasmic ribonucleoprotein granules such as stress granules and those seeded by the aggregation of specific ASO-binding proteins such as FUS/TLS (FUS) and PSF/SFPQ (PSF). Further investigation into the basis for ASO-FUS binding illustrated the importance of ASO backbone and hydrophobic 2' sugar modifications and revealed that the C-terminal region of FUS is sufficient to retain ASOs in cellular foci. Taken together, the results of this study demonstrate that affinities of various nucleic acid binding domains for ASO depend on chemical modifications and further demonstrate how ASO-protein interactions influence the localization of ASOs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos Antissenso
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Proteína FUS de Ligação a RNA
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Oligonucleotídeos Fosforotioatos
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Fator de Processamento Associado a PTB
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article